2023
Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies
Ketzer F, Klemm L, Robinson M, Loucks C, Arce D, Cosgun K, Kothari S, Müschen M. Separation of B- and T-Cell-Specific Signaling Molecules Prevents Oncogenic Transformation in Lymphoid Malignancies. Blood 2023, 142: 1396. DOI: 10.1182/blood-2023-189221.Peer-Reviewed Original ResearchKinase ZAP70Transcriptional regulationTranscription factorsKinase SykDownstream activationT-cell signaling proteinsCRISPR/Cas9-mediated knockoutComparative proteomic analysisNegative selectionFunction of proteinsWild-type cellsCas9-mediated knockoutCo-expressed proteinsPre-malignant cellsT cell linesCellular fitnessTranscription machinerySLP-76Signaling proteinsMalignant transformationSignal transductionAberrant transcriptionProteomic analysisChIP-qPCRNovel key mechanismCD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling
Sun R, Lee J, Robinson M, Kume K, Cosgun K, Chan L, Leveille E, Geng H, Vykunta V, Shy B, Marson A, Meffre E, Müschen M. CD25 recruits inhibitory phosphatases for feedback control of B-cell receptor signaling. The Journal Of Immunology 2023, 210: 154.23-154.23. DOI: 10.4049/jimmunol.210.supp.154.23.Peer-Reviewed Original ResearchAntigen-experienced B cellsB cellsEarly B cell developmentGerminal centersB cell developmentSpontaneous germinal centersCD25 surface expressionAutoreactive B cellsRole of CD25B cell toleranceB-cell receptor signalingB-cell leukemiaB cell receptorAutoantibody productionCD25Cell toleranceGenetic ablationReceptor signalingBCR signalingOncogenic signalingInhibitorySuccessful initiationSignalingNegative selectionAutoimmunity
2021
Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer
Sadras T, Martin M, Kume K, Robinson ME, Saravanakumar S, Lenz G, Chen Z, Song JY, Siddiqi T, Oksa L, Knapp AM, Cutler J, Cosgun KN, Klemm L, Ecker V, Winchester J, Ghergus D, Soulas-Sprauel P, Kiefer F, Heisterkamp N, Pandey A, Ngo V, Wang L, Jumaa H, Buchner M, Ruland J, Chan WC, Meffre E, Martin T, Müschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Molecular Cell 2021, 81: 2094-2111.e9. PMID: 33878293, PMCID: PMC8239336, DOI: 10.1016/j.molcel.2021.03.043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CD19AutoimmunityB-LymphocytesCalciumCell DifferentiationCell Transformation, NeoplasticEnzyme ActivationHumansImmune ToleranceLymphoma, B-CellMiceModels, GeneticNeoplasm ProteinsNeoplasmsNFATC Transcription FactorsPhosphatidylinositol 3-KinasesProtein BindingReceptors, Antigen, B-CellSignal TransductionSyk KinaseZAP-70 Protein-Tyrosine Kinase
2016
PTEN opposes negative selection and enables oncogenic transformation of pre-B cells
Shojaee S, Chan LN, Buchner M, Cazzaniga V, Cosgun KN, Geng H, Qiu YH, von Minden MD, Ernst T, Hochhaus A, Cazzaniga G, Melnick A, Kornblau SM, Graeber TG, Wu H, Jumaa H, Müschen M. PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nature Medicine 2016, 22: 379-387. PMID: 26974310, PMCID: PMC5178869, DOI: 10.1038/nm.4062.Peer-Reviewed Original ResearchConceptsTrigger cell deathTumor suppressor roleOncogenic transformationCell deathSuppressor rolePTEN inhibitionNegative selection